In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis

Rafael L. Ufret-Vincenty, Laura Quigley, Nancy Tresser, Seong Hee Pak, Ameer Gado, Stefan Hausmann, Kai W. Wucherpfennig, Stefan Brocke

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide-specific T cells that cross-reacted with MBP(87-99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Barr virus (EBV). These low dose viral peptide-specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide-specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen-specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide-specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide-specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.

Original languageEnglish (US)
Pages (from-to)1725-1738
Number of pages14
JournalJournal of Experimental Medicine
Volume188
Issue number9
DOIs
StatePublished - Nov 2 1998

Keywords

  • Antigenic peptide
  • Autoimmunity
  • Cross-reactivity
  • Experimental autoimmune encephalomyelitis
  • Molecular mimicry

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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